The objective of the proposed research is development and optimization of cryogen spray cooling (CSC) in conjunction with laser irradiation to protect superficial skin structures from thermal injury, while achieving photothermal destruction of subsurface targeted blood vessels for successful treatment of hypervascular cutaneous malformations such as port wine stains (PWS) and hemangiomas. We propose to: 1) develop mathematical models, and perform experiments utilizing in-vitro and in-vivo phantoms to optimize CSC and laser irradiation parameters; and 2) design and construct a prototype instrument to a) determine the depth of subsurface targeted blood vessels and an individual patient basis to select optimum CSC and laser irradiation parameters; and b) incorporate a solenoid valve, and an optical fiber for delivery of the cryogen and laser light respectively. PWS is a congenital, progressive hypervascular malformation of the dermis. PWS should not be considered a cosmetic problem per se but a disease with potentially devastating psychological and physical complications. Laser irradiation has offered a superior therapeutic approach due to the ability to photo coagulate PWS blood vessels. However, non-specific photon absorption can result in irreversible epidermal thermal injury. Furthermore, only a small proportion of patients obtain 100% fading of their PWS even after undergoing multiple laser treatments. Improved therapeutic outcome in many patients is expected from the development of laser systems that can deliver relatively high light fluences. However, higher laser light fluences also result in more heat generated in the epidermis. When applied in conjunction with laser irradiation. CSC offers a means to protect the superficial epidermis while still achieving photocoagulation of subsurface targeted blood vessels. Hemangiomas are congenital vascular tumors that enlarge by rapid cellular proliferation. They differ from vascular malformations, such as PWS, in that they are not collections of dilated vessels, but instead, consist of plump, proliferating endothelial cells that almost entirely occupy the dermis. Due to psychological and social factors, as well as functional impairments such as difficulty in eating, visual and breathing obstructions, early treatment is often recommended. Although, laser irradiation is a preferred method of therapy, a particularly problematic complication that can occur is thermally induced damage to the epidermis and papillary dermis. CSC in conjunction with laser irradiation may offer a means to protect the superficial tissue structures while achieving deep photocoagulation of hemangiomas.